Peptide fusion improves prime editing efficiency

Minja Velimirovic, Larissa C. Zanetti, Max W. Shen, James D. Fife, Lin Lin, Minsun Cha, Ersin Akinci, Danielle Barnum, Tian Yu and Richard I. Sherwood ()
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Minja Velimirovic: Brigham and Women’s Hospital and Harvard Medical School
Larissa C. Zanetti: Brigham and Women’s Hospital and Harvard Medical School
Max W. Shen: Broad Institute of Harvard and MIT
James D. Fife: Brigham and Women’s Hospital and Harvard Medical School
Lin Lin: Hubrecht Institute
Minsun Cha: Brigham and Women’s Hospital and Harvard Medical School
Ersin Akinci: Brigham and Women’s Hospital and Harvard Medical School
Danielle Barnum: Brigham and Women’s Hospital and Harvard Medical School
Tian Yu: Brigham and Women’s Hospital and Harvard Medical School
Richard I. Sherwood: Brigham and Women’s Hospital and Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract Prime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, the Peptide Self-Editing sequencing assay (PepSEq), to measure how fusion of 12,000 85-amino acid peptides influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites. Top prime-enhancing peptides function by increasing translation efficiency and serve as broadly useful tools to improve prime editing efficiency.

Date: 2022
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DOI: 10.1038/s41467-022-31270-y

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